Anticoagulation Use and Endovascular Thrombectomy in Patients with Large Core Stroke: A Secondary Analysis of the SELECT2 Trial.

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4-6] vs MM 5 [4-6], adjusted generalized odds ratio 0.89 [0.53-1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3-6] vs MM 5 [4-6], adjusted generalized odds ratio 1.87 [1.45-2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024.

Current State of Evidence for Neuroimaging Paradigms in Management of Acute Ischemic Stroke.

Stroke is the chief differential diagnosis in patient presenting to the emergency room with abrupt onset focal neurological deficits. Neuroimaging, including non-contrast computed tomography (CT), magnetic resonance imaging (MRI), vascular and perfusion imaging, is a cornerstone in the diagnosis and treatment decision-making. This review examines the current state of evidence behind the different imaging paradigms for acute ischemic stroke diagnosis and treatment, including current recommendations from the guidelines. Non-contrast CT brain, or in some centers MRI, can help differentiate ischemic stroke and intracerebral hemorrhage (ICH), a pivotal juncture in stroke diagnosis and treatment algorithm, especially for early window thrombolytics. Advanced imaging such as MRI or perfusion imaging can also assist making a diagnosis of ischemic stroke versus mimics such as migraine, Todd's paresis, or functional disorders. Identification of medium-large vessel occlusions with CT or MR angiography triggers consideration of endovascular thrombectomy (EVT), with additional perfusion imaging help identify salvageable brain tissue in patients who are likely to benefit from reperfusion therapies, particularly in the ≥6 h window. We also review recent advances in neuroimaging and ongoing trials in key therapeutic areas and their imaging selection criteria to inform the readers on potential future transitions into use of neuroimaging for stroke diagnosis and treatment decision making. ANN NEUROL 2024;95:1017-1034.

Talking treats: A qualitative study to understand the importance of treats in the pet-caregiver relationship.

Treats are a prevalent aspect of pet care, frequently given by dog and cat caregivers for varying reasons. However, recommendations of reducing or eliminating treat feeding poses a common challenge, leading to potential non-adherence surrounding weight management practices. To explore caregivers' perceptions and experiences surrounding treat feeding, we conducted five online focus groups with 24 dog and cat caregivers, recruited via an infographic shared on social media using snowball sampling. NVivo12© was used to organize and analyze verbatim transcripts using inductive thematic analysis. Outcomes illustrated three major themes: 1) the role of treats as an important tool for caregivers; 2) considerations for treat selection and provision; and 3) caregivers' need for more and better information and support related to treats. Participants emphasized the importance of treats for managing behaviours, health-related activities, and enhancing the pet-caregiver relationship. Results suggest that the diverse and valued applications of treats, caregivers' satisfaction associated with treat-giving, and perceived lack of guidance surrounding treats may present challenges for caregivers in reducing treat feeding with their pets. Findings highlight opportunities to enhance the available resources that can empower both veterinary professionals and caregivers to make well-informed decisions and foster sustainable changes in treat feeding practices to support weight management and overall health. Such considerations can improve client compliance with veterinary recommendations, to promote companion animal health and well-being while fostering the human-animal bond.

18F-FDG Dedicated Breast PET Complementary to Breast MRI for Evaluating Early Response to Neoadjuvant Chemotherapy.

Purpose To compare quantitative measures of tumor metabolism and perfusion using fluorine 18 (18F) fluorodeoxyglucose (FDG) dedicated breast PET (dbPET) and breast dynamic contrast-enhanced (DCE) MRI during early treatment with neoadjuvant chemotherapy (NAC). Materials and Methods Prospectively collected DCE MRI and 18F-FDG dbPET examinations were analyzed at baseline (T0) and after 3 weeks (T1) of NAC in 20 participants with 22 invasive breast cancers. FDG dbPET-derived standardized uptake value (SUV), metabolic tumor volume, and total lesion glycolysis (TLG) and MRI-derived percent enhancement (PE), signal enhancement ratio (SER), and functional tumor volume (FTV) were calculated at both time points. Differences between FDG dbPET and MRI parameters were evaluated after stratifying by receptor status, Ki-67 index, and residual cancer burden. Parameters were compared using Wilcoxon signed rank and Mann-Whitney U tests. Results High Ki-67 tumors had higher baseline SUVmean (difference, 5.1; P = .01) and SUVpeak (difference, 5.5; P = .04). At T1, decreases were observed in FDG dbPET measures (pseudo-median difference T0 minus T1 value [95% CI]) of SUVmax (-6.2 [-10.2, -2.6]; P < .001), SUVmean (-2.6 [-4.9, -1.3]; P < .001), SUVpeak (-4.2 [-6.9, -2.3]; P < .001), and TLG (-29.1 mL3 [-71.4, -6.8]; P = .005) and MRI measures of SERpeak (-1.0 [-1.3, -0.2]; P = .02) and FTV (-11.6 mL3 [-22.2, -1.7]; P = .009). Relative to nonresponsive tumors, responsive tumors showed a difference (95% CI) in percent change in SUVmax of -34.3% (-55.9%, 1.5%; P = .06) and in PEpeak of -42.4% (95% CI: -110.5%, 8.5%; P = .08). Conclusion 18F-FDG dbPET was sensitive to early changes during NAC and provided complementary information to DCE MRI that may be useful for treatment response evaluation. Keywords: Breast, PET, Dynamic Contrast-enhanced MRI Clinical trial registration no. NCT01042379 Supplemental material is available for this article. © RSNA, 2024.

Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles.

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial.

BACKGROUND: Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients. METHODS: SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand. Patients aged 18-85 years with ischaemic stroke due to proximal occlusion of the internal carotid artery or of the first segment of the middle cerebral artery, showing large ischaemic core on non-contrast CT (Alberta Stroke Program Early Computed Tomographic Score of 3-5 [range 0-10, with lower values indicating larger infarctions]) or measuring 50 mL or more on CT perfusion and MRI, were randomly assigned, within 24 h of ischaemic stroke onset, to thrombectomy plus medical care or to medical care alone. The primary outcome for this analysis was the ordinal modified Rankin Scale (range 0-6, with higher scores indicating greater disability) at 1-year follow-up in an intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT03876457) and is completed. FINDINGS: The trial was terminated early for efficacy at the 90-day follow-up after 352 patients had been randomly assigned (178 to thrombectomy and 174 to medical care only) between Oct 11, 2019, and Sept 9, 2022. Thrombectomy significantly improved the 1-year modified Rankin Scale score distribution versus medical care alone (Wilcoxon-Mann-Whitney probability of superiority 0·59 [95% CI 0·53-0·64]; p=0·0019; generalised odds ratio 1·43 [95% CI 1·14-1·78]). At the 1-year follow-up, 77 (45%) of 170 patients receiving thrombectomy had died, compared with 83 (52%) of 159 patients receiving medical care only (1-year mortality relative risk 0·89 [95% CI 0·71-1·11]). INTERPRETATION: In patients with ischaemic stroke due to a proximal occlusion and large core, thrombectomy plus medical care provided a significant functional outcome benefit compared with medical care alone at 1-year follow-up. FUNDING: Stryker Neurovascular.

Endovascular Thrombectomy Treatment Effect in Direct vs Transferred Patients With Large Ischemic Strokes: A Prespecified Analysis of the SELECT2 Trial.

Importance: Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT). Objective: To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes. Design, Setting, and Participants: This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as well as an Alberta Stroke Program Early CT Score (ASPECTS) of 3 to 5, core of 50 mL or greater on imaging, or both. Patients were enrolled between October 2019 and September 2022 from 31 EVT-capable centers in the US, Canada, Europe, Australia, and New Zealand. Data were analyzed from August 2023 to January 2024. Interventions: EVT vs MM. Main Outcomes and Measures: Functional outcome, defined as modified Rankin Scale (mRS) score at 90 days with blinded adjudication. Results: A total of 958 patients were screened and 606 patients were excluded. Of 352 enrolled patients, 145 (41.2%) were female, and the median (IQR) age was 66.5 (58-75) years. A total of 211 patients (59.9%) were transfers, while 141 (40.1%) presented directly. The median (IQR) transfer time was 178 (136-230) minutes. The median (IQR) ASPECTS decreased from the referring hospital (5 [4-7]) to an EVT-capable center (4 [3-5]). Thrombectomy treatment effect was observed in both directly presenting patients (adjusted generalized odds ratio [OR], 2.01; 95% CI, 1.42-2.86) and transferred patients (adjusted generalized OR, 1.50; 95% CI, 1.11-2.03) without heterogeneity (P for interaction = .14). Treatment effect point estimates favored EVT among 82 transferred patients with a referral hospital ASPECTS of 5 or less (44 received EVT; adjusted generalized OR, 1.52; 95% CI, 0.89-2.58). ASPECTS loss was associated with numerically worse EVT outcomes (adjusted generalized OR per 1-ASPECTS point loss, 0.89; 95% CI, 0.77-1.02). EVT treatment effect estimates were lower in patients with transfer times of 3 hours or more (adjusted generalized OR, 1.15; 95% CI, 0.73-1.80). Conclusions and Relevance: Both directly presenting and transferred patients with large ischemic stroke in the SELECT2 trial benefited from EVT, including those with low ASPECTS at referring hospitals. However, the association of EVT with better functional outcomes was numerically better in patients presenting directly to EVT-capable centers. Prolonged transfer times and evolution of ischemic change were associated with worse EVT outcomes. These findings emphasize the need for rapid identification of patients suitable for transfer and expedited transport. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Reporting perceived capability, motivations, and barriers to reducing treat feeding amongst dog and cat caregivers.

Obesity remains a significant concern for dogs and cats, and reducing or eliminating treats is commonly recommended as a strategy for weight management. Caregivers can struggle with adherence to such dietary recommendations. Previous research suggests caregivers are reluctant to reduce treats but there is limited understanding of the underlying factors contributing to these behaviours and decisions. The objective of this study was to explore caregivers' motivations and barriers to reducing treat feeding, and their reported capability to do so. An online questionnaire including multiple choice and Likert scale questions was disseminated to dog and cat caregivers (n=1053) primarily from Canada and the USA from September to November 2021. Caregivers commonly expressed a wide range of motivations to reduce treat feeding with their pet, though barriers to reducing treat feeding were less defined. Changing their pet's routine was a reported barrier by more than 30% of respondents and was predictive of caregivers finding reducing treat giving to be difficult (OR=1.67, p=0.017). Results from multivariable logistic regression also revealed that caregivers who consider their companion animal to be obese as more likely to perceive reducing treats to be difficult. The results highlight the role of treats in the relationship and routine of caregivers' and their pets, and the importance of considering the individualised needs and circumstance of the caregiver and pet in veterinary discussions surrounding reducing treat feeding. Identifying these perspectives can improve self-efficacy with veterinary nutrition recommendations surrounding treats.

Cat caregivers' perceptions, motivations, and behaviours for feeding treats: A cross sectional study.

There is an abundance of research focusing on the nutritional needs of the cat, though aspects surrounding treat feeding have received far less attention. Feeding practices have the potential to cause nutrient imbalances and adverse health outcomes, including obesity. The objective of this study was to identify and describe the perceptions, motivations, and behaviours surrounding treats, and factors that influence treat feeding by cat caregivers. A 56-question online survey was disseminated to cat caregivers (n = 337) predominantly from Canada and the USA to collect data regarding caregiver and cat demographics, the pet-caregiver relationship, perceptions surrounding treats, and feeding practices and behaviours. Descriptive statistics, chi-square tests, Kruskal-Wallis one-way ANOVA, Wilcoxon signed-rank tests, and multivariable logistic regression models were used to analyze the survey data. Caregivers had varying interpretations of the term 'treat' and how treats relate to the primary diet, and these perceptions appeared to influence the quantity of treats provided. Aspects relating to the human-animal bond were highlighted as an important factor in decisions and behaviours surrounding treat feeding in our results. Though the majority (224/337, 66%) of respondents indicated they monitor their pet's treat intake, using an eyeball estimate was the most frequent (139/337, 41%) method reported to measure treats. Multivariable logistic regression results revealed feeding jerky, bones, dental treats, and table scraps in select frequencies were predictive of caregivers perceiving their cat as overweight/obese. Results provide valuable new insights to cat caregiver feeding practices and perceptions of treats and can be used to inform veterinary nutrition support to caregivers. More research is warranted to further our understanding and ensure that cats receive optimal nutrition and care.

Is thrombectomy indicated in all ischemic stroke with large vessel occlusion?

PURPOSE OF REVIEW: Purpose of this topical review is to examine the current randomized and nonrandomized evidence evaluating endovascular thrombectomy (EVT) in selected patient populations with acute ischemic stroke due to large vessel occlusions. RECENT FINDINGS: After establishing EVT as the first-line treatment in patients with large vessel occlusions and limited ischemic changes on neuroimaging, recent trials successfully demonstrated efficacy and safety in patients with large core strokes and those with basilar occlusions up to 24 h of last known well. Nonrandomized evidence in patients with mild stroke severity, baseline disability, medium and distal vessel occlusions and time from last known well >24 h also suggested potential benefit of EVT in selected patients. Further randomized evidence will help establish EVT efficacy and safety in these populations. SUMMARY: EVT is established as the de-facto treatment of choice in a significant proportion of patients presenting with acute ischemic stroke due to a large vessel occlusion and has shown potential benefits in additional patient subgroups. A rigorous risk-benefit assessment and discussions with patients and their families in the absence of randomized evidence should help facilitate an informed, individualized decision-making process for this revolutionary treatment in peripheral patient subgroups with limited evidence.

Primary extranodal lymphomas: five-year experience from a tertiary care center of North India.

BACKGROUND: Primary extranodal lymphomas (pENL) are lymphomas with minimal nodal involvement and dominant extranodal disease. We aimed to study the prevalence and clinicopathological characteristics of pENL presenting at our center over 5 years from January 2015 to January 2020. METHODS: This is a cross-sectional study of pENL patients in which relevant clinical and laboratory data was collected including demography, site, stage, international prognostic index-revised, imaging findings, hematological, and biochemical parameters and comorbidities including underlying immunodeficiency. The paraffin blocks were subjected to routine hematoxylin and eosin stain and immunohistochemistry with standard lymphoma panel. RESULTS: Of 341 lymphomas, 73 (21.4%) were pENL with commonest site being gastrointestinal tract (31.5%) followed by head and neck (23.2%) and soft tissues (9.6%). Diffuse large B-cell lymphoma (DLBCL) (39.7%) was the commonest histological type (germinal center type-48%, nongerminal center-52%) followed by marginal zone lymphomas (MZL) (23.3%) and primary CNS lymphoma (8.2%). Primary breast lymphoma, primary bone marrow lymphoma, and follicular lymphoma constituted 4.1, 5.4, and 4.1% of pENL, respectively. There was a case of high grade B cell lymphoma of ileum with features intermediate between DLBCL and Burkitt. Other unusual pENL were anaplastic DLBCL of tonsils, DLBCLs of bone marrow with M band, MZL of base of tongue, Richter's transformation of tonsillar small lymphocytic lymphoma, and follicular lymphoma presenting as pericardial mass. Of 12 cases of T-non-Hodgkin lymphoma, commonest were mycosis fungoides (4/12) followed by mediastinal T-lymphoblastic lymphoma (2/12) and peripheral T-cell lymphoma (2/12). CONCLUSION: pENL has unique clinical presentation depending on the location with site-specific distribution of histological subtypes.

Novel Curcumin Analogue L6H4 in Treating Liver Fibrosis and Type 2 Diabetes.

Purpose: The objective of this study was to evaluate the therapeutic efficacy of the curcumin analogue L6H4 in attenuating liver fibrosis and alleviating insulin resistance in streptozotocin-induced diabetic rats. Methods: Male Sprague-Dawley rats were fed a high-fat diet to induce insulin resistance, followed by streptozotocin injection to induce diabetes. The rats were then treated with L6H4 for eight weeks. Body weight, metabolic parameters, liver function, and liver histopathology were evaluated. Immunohistochemistry was performed to assess the expression of TGF-ß1, TIMP-2, and MMP-2 in liver tissues. Statistical analysis was conducted using one-way ANOVA and Spearman rank correlation test. Results: L6H4 treatment effectively reversed the weight gain associated with a high-fat diet and improved metabolic parameters in diabetic rats. Liver function markers, such as ALT and AST, were reduced after L6H4 treatment. Histological analysis showed improved liver morphology and reduced fibrosis in L6H4-treated rats. Electron microscopy revealed improved ultrastructural features of hepatocytes. Immunohistochemistry demonstrated downregulation of TGF-ß1 and TIMP-2 expression and restoration of MMP-2 expression in the liver tissue of L6H4-treated rats. Correlation analysis showed a significant positive correlation between TGF-ß1 and TIMP-2 expression. Conclusion: The findings suggest that L6H4 has therapeutic potential in attenuating liver fibrosis and alleviating insulin resistance in streptozotocin-induced diabetic rats. The hepatoprotective effect of L6H4 may be attributed to its anti-inflammatory properties and its ability to target molecules involved in fibrosis. Further research is warranted to explore the potential of L6H4 as a treatment option for nonalcoholic fatty liver disease and type 2 diabetes.

Dog caregivers' perceptions, motivations, and behaviours for feeding treats: A cross sectional study.

Treats are commonly fed by most dog caregivers and can constitute a significant proportion of a dog's diet, potentially contributing to obesity. Feeding aspects related to treats specifically, remain underexplored. An e-survey was voluntarily completed by 716 dog caregivers predominantly from Canada and the USA to identify and describe caregivers' perceptions, motivations, and behaviours surrounding treats, and factors that influence decisions about feeding treats. Survey responses were analyzed using descriptive statistics, chi-square tests, Kruskal-Wallis one-way ANOVA, and Wilcoxon signed-rank tests. Multivariable logistic regression analyses were performed to analyze (1) measurement methods associated with monitoring treat intake, and (2) frequency of feeding different types of treats with perceiving dog as overweight/obese. Most caregivers considered the term 'treat' in a nutritional context, but respondents expressed mixed perceptions of how they consider treats in relation to their dog's primary diet. Alongside training and sports activities, aspects relating to the human-animal bond were highly reported to influence decisions surrounding treats. Most respondents were motivated to provide treats because it makes their pet happy, and to strengthen the bond with their dog, and nearly 40% of caregivers frequently feed treats to show love to their dog. Human food and table scraps were frequently fed by 30-40% of caregivers and feeding human food weekly was predictive of caregivers perceiving their dog to be overweight/obese (OR=2.24, p = 0.007). Caregivers estimated treats to account for a median of 15% of their dog's total diet, based on estimated quantity. Caregivers who reported using a measuring cup/scoop to measure their dog's treats were more likely to monitor their dog's treat intake (OR=3.38, p = 0.002). Most caregivers monitor their dog's body condition (60%) or consider their dog's recent activity level (43%) to decide on the amount of treats to feed; only 22% of caregivers reported veterinary advice to support their decisions on the amount of treats to feed. Findings from this research offer new insights to dog caregiver feeding habits and their perceptions of treats in relation to the canine diet. These results can be used to inform veterinary counselling strategies and caregiver education initiatives to promote animal health and well-being.

Outcomes of adjunct posterior wall isolation in atrial fibrillation patients with cardiac implantable electronic devices.

BACKGROUND: Although pulmonary vein isolation (PVI) remains the cornerstone of catheter ablation of atrial fibrillation (AF), several studies have illustrated clinical benefits associated with PVI with posterior wall isolation (PWI). METHODS: This retrospective study investigated the outcomes of PVI alone versus PVI+PWI performed using the cryoballoon in patients with cardiac implantable electronic devices (CIEDs) and paroxysmal AF (PAF) or persistent AF (PersAF). RESULTS: Acute PVI was achieved in all patients using cryoballoon ablation. Compared to PVI alone, PVI+PWI was associated with longer cryoablation, fluoroscopy, and total procedure times. Adjunct radiofrequency was required to complete PWI in 29/77 patients (37.7%). Adverse events were similar with PVI alone versus PVI+PWI. But at 24 ± 7 months of follow-up, not only cryoballoon PVI+PWI was associated with improved freedom from recurrent AF (74.3% vs. 46.0%, P = .007) and all atrial tachyarrhythmias (71.4% vs. 38.1%, P = .001) in patients with PersAF, cryoballoon PVI+PWI also yielded greater freedom from AF (88.1% vs. 63.7%, P = .003) and all atrial tachyarrhythmias (83.3% vs. 60.8%, P = .008) in those with PAF. Additionally, PVI+PWI was associated with higher reductions in atrial tachyarrhythmia burden (97.9% vs. 91.6%, P < .001), need for cardioversion (5.2% vs. 23.6%, P < .001) and repeat catheter ablation (10.4% vs. 26.1%, P = .005), and a longer time-to-arrhythmia recurrence (16 ± 6 months vs. 8 ± 5 months, P < .001) in both PersAF and PAF patients. CONCLUSION: In CIED patients with PersAF or PAF, cryoballoon PVI+PWI is associated with a greater freedom from recurrent AF and atrial tachyarrhythmias, as compared to PVI alone during long-term follow-up.

Pulmonary Vein Isolation With and Without Posterior Wall Isolation in Paroxysmal Atrial Fibrillation: IMPPROVE-PAF Trial.

BACKGROUND: Prior studies have demonstrated clinical benefits associated with cryoballoon pulmonary vein isolation (PVI) and concomitant posterior wall isolation (PWI) in patients with persistent atrial fibrillation (AF). However, the role for this approach in patients with paroxysmal atrial fibrillation (PAF) remains unclear. OBJECTIVES: This study investigated the acute and long-term outcomes of PVI vs PVI+PWI using cryoballoon in patients with symptomatic PAF. METHODS: This retrospective study (NCT05296824) examined the outcomes of cryoballoon PVI (n = 1,342) vs cryoballoon PVI+PWI (n = 442) in patients with symptomatic PAF during long-term follow-up. Using the nearest-neighbor method, a 1:1 matched sample of patients receiving PVI alone and PVI+PWI was created. RESULTS: The matched cohort consisted of 320 patients (PVI: n = 160; PVI+PWI: n = 160). PVI+PWI was associated with longer cryoablation (23 ± 10 minutes vs 42 ± 11 minutes; P < 0.001) and procedure times (103 ± 24 minutes vs 127 ± 14 minutes; P < 0.001). In 39 (24.4%) of 160 patients, adjunct radiofrequency ablation was required for PVI+PWI. Adverse event rates were similar (PVI 3.8% vs PVI+PWI 1.9%; P = 0.31). Though there were no differences at 12 months, freedom from all atrial arrhythmias (67.5% vs 45.0%; P < 0.001) and AF (75.6% vs 55.0%; P < 0.001) were significantly greater with PVI+PWI vs PVI alone at 39 ± 9 months of follow-up. PVI+PWI was also associated with reduced long-term need for cardioversion (16.9% vs 27.5%; P = 0.02) and repeat catheter ablation (11.9% vs 26.3%; P = 0.001), and emerged as the only significant predictor of freedom from recurrent AF (HR: 2.79; 95% CI: 1.64-4.74; P < 0.001). CONCLUSIONS: Compared with cryoballoon PVI, cryoballoon PVI+PWI appears to be associated with greater freedom from recurrent atrial arrhythmias and AF in patients with PAF during long-term follow-up >3 years.

Teaching Accuracy through Repeated Gamified Echography Training (TARGET): Assessment of an Ultrasound Skill Simulator in Teaching Ultrasound-Guided Needle Placement, a Prospective Observational Study.

The increasing use of ultrasound in veterinary private practice and demand for skilled operators upon graduation has placed an increased burden on the ever-dwindling number of academic radiologists. Simulation-based medical education can help prepare for and consequently reduce this burden, allowing for the acquisition of clinical skills through deliberate practice in a safe, controlled, and low-stakes environment. Ultrasound-guided fine needle placement is the foundation for more advanced interventions such as ultrasound-guided fine needle aspirates and centeses. A reusable novel ultrasound skill simulator consisting of metal targets wired to a circuit and suspended in ballistics gel was created to teach ultrasound-guided fine needle placement. Forty-seven second-year veterinary students watched an instructional video and performed two ultrasound-guided fine needle placement skill tests on the simulator with a period of practice between. Significant improvement in time to task completion (p = .0021) was noted after the period of practice. The majority of student feedback was positive with 89% (42/47) indicating they would use the simulator again to practice and that it should be incorporated into the curriculum, 74% (35/47) indicating their basic skills, knowledge, and confidence using ultrasound improved using the simulator, and 55% (26/47) indicating they could now teach this skill to a peer. The authors suggest further development of this model for ease of manufacture and increased variation in difficulty, and veterinary curriculum incorporation for basic ultrasound-guided fine needle placement training.

Trial of Endovascular Thrombectomy for Large Ischemic Strokes.

BACKGROUND: Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations. METHODS: We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome. RESULTS: The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P<0.001). A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence (relative risk, 2.97; 95% CI, 1.60 to 5.51). Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group. CONCLUSIONS: Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.).

Association of Endovascular Thrombectomy vs Medical Management With Functional and Safety Outcomes in Patients Treated Beyond 24 Hours of Last Known Well: The SELECT Late Study.

Importance: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well. Objective: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well. Design, Setting, and Participants: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well. Interventions: Endovascular thrombectomy or medical management (control). Main Outcomes and Measures: Primary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts. Results: Of 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P < .001) despite increased odds of sICH (10.1% for EVT vs 1.7% for control; IPTW aOR, 10.65; 95% CI, 2.19-51.69; P = .003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P = .047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P = .03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P = .04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P = .02). Conclusions and Relevance: In this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation.

Mediation of Successful Reperfusion Effect through Infarct Growth and Cerebral Edema: A Pooled, Patient-Level Analysis of EXTEND-IA Trials and SELECT Prospective Cohort.

OBJECTIVE: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. METHODS: In a pooled, patient-level analysis of the EXTEND-IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. RESULTS: A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8-48.4), and median midline shift was 0mm (IQR = 0-2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89-4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (ß = -1.19, 95% confidence interval [CI] = -1.51 to -0.88, p < 0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23-0.57, p < 0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86-3.88, p < 0.001) became insignificant (acOR = 1.39, 95% CI = 0.95-2.04, p = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. INTERPRETATION: In this mediation analysis from a pooled, patient-level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023;93:793-804.